The in vitro and in vivo indomethacin release from self-setting bioactive glass bone cement.
The in vivo and in vitro drug release profiles from a self-setting bioactive CaO-SiO2-P2O5 glass bone cement containing indomethacin as a model drug were investigated. The cement containing 2% and 5% indomethacin (IMC) powder hardened within 5 min after mixing with ammonium phosphate buffer. After setting, in vitro drug release from drug-loaded cement pellets in a simulated body fluid (SBF) at pH 7.25 and 37 degrees C continued for two weeks. The hardened cement gradually formed low-crystallinity hydroxyapatite during the drug release test in SBF. An IMC-loaded cement device (2% and 5% drug) was implanted in the subcutaneous tissue on the back of rats. The in vivo IMC release from the cement increased and attained maximum levels (Cmax of 2% and 5% drug-loaded cements was 0.27 and 3.37 micrograms/ml, respectively) at Tmax, 3 and 0.5 d, respectively, upon subcutaneous (s.c.) administration in rats. This suggested that the s.c. administration of the cement provided IMC release for a much longer period than s.c. administration of the solution, and the plasma IMC concentration was dependent on the drug concentration in the cement. The plasma IMC concentration and the area under the curve from 2% and 5% IMC-loaded cements in rats were dependent on the concentration of IMC in the cements. The in vivo IMC concentration in plasma obtained by the deconvolution method was much lower than that delivered in SBF in vitro. Scanning electron microscopy and photomicrographs of cross sections showed that the bioactive bone cement had excellent biocompatibility with the surrounding soft tissues.
Otsuka
M
M
Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Japan. m-otsuka@kobepharma-u.ac.jp
Nakahigashi
Y
Y
Matsuda
Y
Y
Kokubo
T
T
Yoshihara
S
S
Fujita
H
H
Nakamura
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000737:chemistry*; D019540:Area Under Curve; D001672:Biocompatible Materials / Q000737:chemistry; D001682:Biological Availability; D001826:Body Fluids / Q000737:chemistry; D001843:Bone Cements / Q000737:chemistry*; D017610:Calcium Compounds / Q000737:chemistry; D003460:Crystallization; D062109:Dermatologic Surgical Procedures; D016503:Drug Delivery Systems; D004343:Drug Implants; D017886:Durapatite / Q000737:chemistry; D005898:Glass / Q000737:chemistry*; D006244:Hardness; D007213:Indomethacin / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000737:chemistry*; D008297:Male; D008855:Microscopy, Electron, Scanning; D010087:Oxides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000737:chemistry; D012867:Skin / Q000648:ultrastructure; D013314:Stress, Mechanical; D013499:Surface Properties; D013997:Time Factors; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D001843:Bone Cements; D017610:Calcium Compounds; D004343:Drug Implants; D010087:Oxides; D010710:Phosphates; C024788:ammonium phosphate; D012822:Silicon Dioxide; D017886:Durapatite; C016538:lime; D007213:Indomethacin